The present invention relates to a process for the production of prostaglandin intermediates.
A prostaglandin has a basic skeleton represented by the formula (c): ##STR1##
A prostaglandin having a double bond between the carbon atoms of the 5 and 6 positions (referred to as the C.sub.5 -C.sub.6 position hereinafter, and this compound is hereinafter referred to as .DELTA..sup.5 -PG), of which carbon atoms are located at the 2nd and 3rd positions counted from the carbon atom of the 5 membered ring having the .alpha.-chain linked thereto, has the cis- and trans-isomers. As the compound having a physiological activity is mainly a cis-isomer, it is important from the industrial standpoint to produce the cis-isomer in improved yield.
Up to this time the introduction of the .alpha.-chain in the production of prostaglandins has been achieved as illustrated is the following scheme using Wittig reaction in which an ylide reacts with the lactol (d) having the .omega.-chain introduced therein: ##STR2## wherein X' is a protective group.
In order to obtain .DELTA..sup.5 -PGs which have a double bond between the C.sub.5 -C.sub.6 positions the lactol (d) is reacted with the ylide obtained from (4-carboxybutyl)triphenylphosphonium bromide, which is usually used in the form of a sodium salt of carboxylic acid produced by the reaction of (4-carboxybutyl)triphenylphosphonium bromide with sodium methylsulfinyl carbanion being obtainable from DMSO and NaH: EQU Ph.sub.3 P.sup.+ C(Br.sup.-)H.sub.2 (CH.sub.2).sub.3 COOH.fwdarw.Ph.sub.3 P.dbd.CH(CH.sub.2).sub.3 COO.sup.- Na.sup.+
This ylide is reacted with the lactol in a solvent such as DMSO and the like. The reaction temperature is generally in the range from the ambient temperature to 70.degree. C.
According to the above process which has conventionally been used for the introduction of the .alpha.-chain, the trans type .DELTA..sup.5 -PGs (referred to as .DELTA..sup.5 -trans-PGs) is present in the resultant product at a rate of about 10% by weight. Consequently, it is absolutely necessary to purify the product when it is used as a starting material for drugs. In such purification the more impurity makes the less productivity.